Charge-dependent regulation of NADPH oxidase activities in intact and subcellular systems of polymorphonuclear leukocytes

Miyahara, Masanobu; Okimasu, Eiji; Uchida, Hidetsugu; Eisuke, F. Sato; Yamamoto, Masazumi; Utsumi, Kozo

doi:10.1016/s0005-2728(88)80007-0

Cited by 7 publications

(5 citation statements)

References 35 publications

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“…In this respect, there is a possibility that the inhibition of these enzymes may be due to changes in the local charge of membranous proteins. This assumption can be supported with the results demonstrated by Miyahara et al which suggest that a charged moiety of the neutrophils play a key role in metabolic stimulation (28,29). They showed that the inhibition and activation of super oxide generation by leukocytes manipulated by anionic and cationic agents.…”

Section: Discussionsupporting

confidence: 63%

Action sites of antiallergic drugs on human neutrophils.

1990

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Abstract-Sites of the inhibitory action of antiallergic drugs (azelastine, oxatomide, tranilast, repirinast and amlexanox) on human neutrophils were investigated by measuring leukotriene B4 formation, arachidonic acid release and superoxide generation. Results obtained in this study were as follows: (1) Formations of leukotriene B4 by neutrophils activated with a calcium ionophore (A23187) were effectively inhibited by all types of antiallergic drugs examined here, although the required concentrations were within a range of 20-200 /tM. (ii) Releases of arachidonic acid from activated cells were diminished by azelastine and oxatomide that were classified as basic antiallergic drugs. On the contrary, acidic antiallergic agents including repirinast, amlexanox and tranilast enhanced the arachidonic acid liberation. (iii) Generations of superoxide from neutrophils activated with either phorbol 12-myristate 13-acetate or n-formyl-methionyl-leucyl-phenylalanine were effectively diminished only by the basic antiallergic drugs.

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Section: Discussionsupporting

confidence: 63%

Action sites of antiallergic drugs on human neutrophils.

1990

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“…This translocation is staurosporine-insensitive and can be dissociated from the process of phosphorylation, which is markedly inhibited by staurosporine. (5) The finding that the phosphorylation of p47phox and p67phox does not correlate with the translocation and activation of NADPH oxidase might be explained by assuming either that phosphorylation is not the only modification of the cytosolic proteins that promotes their translocation, as proposed by Miyahara [50] and Heyworth and Badway [28], or that protein translocation and NADPH oxidase activation are regulated by the phosphorylation of a threshold number of sites in each molecule of p47phox and p67phox.…”

Section: Discussionmentioning

confidence: 99%

Relationship between phosphorylation and translocation to the plasma membrane of p47phox and p67phox and activation of the NADPH oxidase in normal and Ca2+-depleted human neutrophils

Dusi¹,

Bianca²,

Grzeskowiak³

et al. 1993

Biochemical Journal

115

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Stimulation of neutrophils with different agonists activates a latent multicomponent NADPH oxidase that reduces molecular oxygen to superoxide anion. Evidence has accumulated that phosphorylation of p47phox (the 47 kDa cytosolic phagocyte oxidase factor) and translocation of the two cytosolic components p47phox and p67phox are essential steps in the activation of NADPH oxidase in response to phorbol esters. We analysed the relationships between activation of the NADPH oxidase and phosphorylation and translocation of p47phox and p67phox in normal and Ca(2+)-depleted neutrophils stimulated by the receptor-mediated agonists formyl-methionyl-leucyl-phenylalanine and concanavalin A. The results produced the following conclusions: (1) Translocation of p47phox and p67phox is an essential mechanism for activation of the NADPH oxidase. (2) A continuous translocation of p47phox and p67phox is necessary to maintain the NADPH oxidase in an activated state. (3) Only a fraction of p47phox and p67phox translocated to the plasma membrane is functional for the activation of the oxidase. (4) Translocation is independent of protein kinase C, and is linked to transmembrane signalling involving Ca2+ transients and production of lipidic second messengers. However, under some conditions, such as in Ca(2+)-depleted neutrophils, translocation can also occur independently of signalling pathways involving production of second messengers from hydrolysis of phospholipids and Ca2+ transients. (5) Phosphorylation of p47phox and p67phox can be quantitatively dissociated from translocation, as staurosporine markedly inhibits phosphorylation but not translocation. (6) The activity of NADPH oxidase is not correlated with the amounts of the phosphorylated proteins present in the plasma membrane.

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“…In contrast to the activating ability of lipophilic anions such as SDS, arachidonate [3] or phosphatidic acid [6], lipophilic cations have been shown to inhibit NADPH oxidase activation. These include monoalkylamines [7][8][9] and azelastin [10], an antiallergic drug, but they are xenobiotic molecules and the physiological relevence of the phenomenon is unknown. Lambeth's group reported the inhibitory effect of sphinganine, a biogenic amine, Abbreviations used : cell-free system, cell-free system containing cytosol ; cyt.b 558 , cytochrome b 558 ; GTP-γS, guanosine 5h-O-(3-thiotriphosphate) ; semi-recombinant (cell-free) system, cell-free system containing recombinant cytosolic components.…”

Section: Introductionmentioning

confidence: 99%

Spermine suppresses the activation of human neutrophil NADPH oxidase in cell-free and semi-recombinant systems

Ogata

Nishimoto

Uhlinger

et al. 1996

Biochemical Journal

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Spermine, a cellular polyamine, down-regulates O2- generation in human neutrophils stimulated by receptor-linked agonist [Ogata, Tamura and Takeshita (1992) Biochem. Biophys. Res. Commun. 182, 20-26]. In this study, to elucidate the mechanism for the inhibition, the effect of spermine on cell-free activation of the O2- generating enzyme (NADPH oxidase) was examined. Spermine suppressed the SDS-induced activation of NADPH oxidase in a dose-dependent manner with an IC50 of 18 microM. The inhibition was specific for spermine over its precursor amines, spermidine and putrescine. Spermine did not alter the Km for NADPH or the optimal concentration of SDS for activation. The amine was inhibitory only when added before activation, indicating that it affects the activation process rather than the enzyme's activity. An increased concentration of cytosol partly prevented the inhibition by spermine. In semi-recombinant cell-free system, spermine inhibited the activation of NADPH oxidase as effectively as in the cell-free system (IC50 = 13 microM). Pretreatment of each recombinant cytosolic component with spermine revealed that they (especially p67phox) are sensitive to spermine. These results suggest that spermine interacts with cytosolic component(s) and impairs the assembly of NADPH oxidase.

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Charge-dependent regulation of NADPH oxidase activities in intact and subcellular systems of polymorphonuclear leukocytes

Cited by 7 publications

References 35 publications

Action sites of antiallergic drugs on human neutrophils.

Action sites of antiallergic drugs on human neutrophils.

Relationship between phosphorylation and translocation to the plasma membrane of p47phox and p67phox and activation of the NADPH oxidase in normal and Ca2+-depleted human neutrophils

Spermine suppresses the activation of human neutrophil NADPH oxidase in cell-free and semi-recombinant systems

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